Choline O-acetyltransferase

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{{STRUCTURE_2fy3| PDB=2fy3 | SIZE=350| SCENE= |right|CAPTION=Human choline O-acetyltransferase complex with choline, [[2fy3]] }}
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<StructureSection load='2fy3' size='350' side='right' caption='Human choline O-acetyltransferase complex with choline (PDB entry [[2fy3]])' scene='46/467280/Cv/1'>
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__TOC__
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== Function ==
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'''Choline O-acetyltransferase''' (ChaT) catalyzes the synthesis of acetyl-CoA and choline to form the neurotransmitter acetylcholine. ChaT is found in nerve terminals.
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'''Choline acetyltransferase''' (ChAT) catalyzes the synthesis of acetylcholine (ACh) from the precursors choline and acetyl-CoA in cholinergic neurons. The post-translational phosphorylation of ChAT at Ser440 and Thr456 regulate its activity, binding to plasma membrane and interaction with other proteins<ref>PMID:12675142</ref>.
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{{TOC limit|limit=2}}
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== Disease ==
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Abnormalities of ChAT in the brain have been demonstrated in schizophrenia and sudden infant death syndrome<ref>PMID:10594838</ref>. Mutations in human ChaT are linked to congenital myasthenic syndrome<ref>PMID:12548525</ref>.
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== Relevance ==
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Greater activity and higher ChAT levels in the hippocampus are associated with better performance on hippocampus-based learning and memory tasks<ref>PMID:25930215</ref>. The concentration of ChaT is reduced in brains of Alzheimer's Disease and ALS patients<ref>PMID:23840379</ref>.
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== Structural highlights ==
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Human ChaT contains 2 domains: <scene name='46/467280/Cv/6'>substrate-binding and catalytic domain</scene>. The <scene name='46/467280/Cv/7'>active site is a tunnel in which acetyl-CoA is bound at the surface</scene> and the <scene name='46/467280/Cv/8'>choline at the interior pocket</scene>.<ref>PMID:17144655</ref>
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</StructureSection>
== 3D Structures of choline O-acetyltransferase ==
== 3D Structures of choline O-acetyltransferase ==
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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[[1q6x]], [[1t1u]] – ChaT – rat
 
[[2fy2]] – hChaT – human
[[2fy2]] – hChaT – human
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[[2fy4]] – hChaT + CoA
[[2fy4]] – hChaT + CoA
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[[2fy5]] – hChaT + CoA derivative
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[[2fy5]] – hChaT + CoA derivative<br />
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[[7amd]] - hChaT + pyridine derivative<br />
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[[1q6x]], [[1t1u]] – ChaT – rat
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== References ==
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<references/>
[[Category:Topic Page]]
[[Category:Topic Page]]

Current revision

Human choline O-acetyltransferase complex with choline (PDB entry 2fy3)

Drag the structure with the mouse to rotate

3D Structures of choline O-acetyltransferase

Updated on 07-June-2021


2fy2 – hChaT – human

2fy3 – hChaT + choline

2fy4 – hChaT + CoA

2fy5 – hChaT + CoA derivative
7amd - hChaT + pyridine derivative
1q6x, 1t1u – ChaT – rat

References

  1. ↑ Dobransky T, Rylett RJ. Functional regulation of choline acetyltransferase by phosphorylation. Neurochem Res. 2003 Apr;28(3-4):537-42. PMID:12675142
  2. ↑ Oda Y. Choline acetyltransferase: the structure, distribution and pathologic changes in the central nervous system. Pathol Int. 1999 Nov;49(11):921-37. PMID:10594838
  3. ↑ Maselli RA, Chen D, Mo D, Bowe C, Fenton G, Wollmann RL. Choline acetyltransferase mutations in myasthenic syndrome due to deficient acetylcholine resynthesis. Muscle Nerve. 2003 Feb;27(2):180-7. doi: 10.1002/mus.10300. PMID:12548525 doi:http://dx.doi.org/10.1002/mus.10300
  4. ↑ Hawley WR, Witty CF, Daniel JM, Dohanich GP. Choline acetyltransferase in the hippocampus is associated with learning strategy preference in adult male rats. Behav Brain Res. 2015 Aug 1;289:118-24. doi: 10.1016/j.bbr.2015.04.034. Epub 2015, Apr 27. PMID:25930215 doi:http://dx.doi.org/10.1016/j.bbr.2015.04.034
  5. ↑ Vijayaraghavan S, Karami A, Aeinehband S, Behbahani H, Grandien A, Nilsson B, Ekdahl KN, Lindblom RP, Piehl F, Darreh-Shori T. Regulated Extracellular Choline Acetyltransferase Activity- The Plausible Missing Link of the Distant Action of Acetylcholine in the Cholinergic Anti-Inflammatory Pathway. PLoS One. 2013 Jun 19;8(6):e65936. doi: 10.1371/journal.pone.0065936. Print 2013. PMID:23840379 doi:http://dx.doi.org/10.1371/journal.pone.0065936
  6. ↑ Kim AR, Rylett RJ, Shilton BH. Substrate binding and catalytic mechanism of human choline acetyltransferase. Biochemistry. 2006 Dec 12;45(49):14621-31. PMID:17144655 doi:10.1021/bi061536l

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Michal Harel, Alexander Berchansky

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